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Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells though Wnt/モ-catenin signaling pathway
Zhe Shi 1 (Research worker), Liyuan Zhou2 (Research worker), Yan Zhou3 (Research worker), Xiaoyan Jia1 (Research worker), Xiangjun Yu1 (Graduate student), Xiaohong An4 (Graduate student), Yanzhen Han 1,* (Professor)
1Department of General Surgery and 2Department of Gynaecology, Affiliated Hospital of Hebei Engineering University,
3Department of Nursing, Medical College, Hebei University of Engineering,
4Medical College, Hebei University of Engineering, Jize County People's Hospital
Chloride channel-5 (ClC-5), an important branch of the ClC family, which is involved in the regulation of the proliferation and cell-fate of a variety of cells, including tumor cells. But for now, its function in cholangiocarcinoma (CCA) cells remain enigmatic. Here, we discovered that ClC-5 was up-regulated in CCA tissues and CCA cell lines, while ClC-5 silencing inhibited CCA cell proliferation and induced apoptosis. Further mechanism studies revealed that ClC-5 inhibition could inhibit Wnt/モ-catenin signaling activity and further activate mitochondria apoptotic pathway in CCA cells. Furthermore, rescuing Wnt/モ-catenin signaling activation eliminated the anti-tumor function of ClC-5 knockdown. Together, our research findings illustrated that ClC-5 inhibition plays an anti-tumor role in CCA cells via inhibiting the activity of Wnt/モ-catenin pathway, which in turn activates mitochondrial apoptotic pathway.
Abstract, Accepted Manuscript(in press) [Submitted on March 7, 2022, Accepted on April 28, 2022]
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